Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

Application of a leakage model to assess exfiltration from sewers.

The exfiltration of wastewater from sewer systems in urban areas causes a deterioration of soil and possibly groundwater quality. Beside the simulation of transport and degradation processes in the unsaturated zone and in the aquifer the analysis of the potential impact requires the estimation of quantity and temporal variation of wastewater exfiltration. Exfiltration can be assessed by the application of a leakage model. The hydrological approach was originally developed to simulate the interactions between the groundwater and surface water, it was adapted to allow for modelling of interactions between groundwater and sewer system. In order to approximate the exfiltration specific model parameters infiltration specific parameters were used as a basis. Scenario analysis of the exfiltration in the City of Dresden from 1997 to 1999 and during the flood event in August 2002 shows the variation and the extent of exfiltration rates.